As is well known in the art, when bone is damaged or removed as a result of trauma or surgery, e.g., excision of a tumor, new bone must be regenerated or substituted with a prosthetic skeletal structure, e.g. skeletal prosthesis or construct, or bone substitute material.
Ideally, the prosthetic skeletal structure and/or bone substitute material is derived from calcified autogenic bone material. However, the availability of autogenic bone material and the risks of allogenic bone initiating an immunologic rejection makes the use of natural bone material and structures formed therefrom impractical and expensive for widespread use.
Various alternative materials have thus been developed to form bone substitute compositions and prosthetic skeletal constructs, such as calcium phosphate ceramic materials (i.e. bioceramics), composite materials, bone derivatives, metals, and natural and synthetic polymers.
Calcium phosphate ceramic materials; particularly, hydroxyapatites (HAp) have been widely employed in prosthetic applications for several years. The suitability of HAp as a prosthetic material stems from the facts that it is relatively easy and cheap to manufacture, is nontoxic, and appears to attach well to calcified tissues. Moreover, HAp has the advantageous property of being able to conduct bone apposition, i.e. the bone remodeling process that initially establishes fixation of an uncemented prosthetic structure to adjacent bone.
There are, however, several drawbacks and disadvantages associated with the use of calcium phosphate ceramic materials. Unsintered calcium phosphate prosthetic structures lack sufficient compressive strength and load bearing capacity to be of substantial benefit as a load bearing prosthesis. Further, sintered calcium phosphate ceramics, while able to bear higher compressive forces, are typically too brittle, and not of sufficient porosity to enable cellular and vascular infiltration of the prosthetic structure to the extent necessary to promote remodeling and resorbtion of the structure.
Various metals; particularly, titanium and titanium alloys, have also been widely employed in prosthetic applications. Titanium is, of course, highly biocompatible and exhibits excellent mechanical properties.
Metal and metal composite prostheses are typically rendered more biocompatible by coating the surface thereof with biocompatible materials, such as crystalline HAp, which has the further advantage of being able to serve as a pharmacological carrier medium. However, HAp crystals are not easily grown on the surface of metal prostheses; particularly, under the physiological conditions required to retain biological activity of some bioactive agents used in orthopedic applications.
Various synthetic materials have also been employed to form prosthetic skeletal constructs. The most prevalent synthetic materials that are employed are mixtures of polymethylmetachlorite (PMMA) and benzoilperoxide.
There are similarly several drawbacks and disadvantages associated with the use of synthetic materials. A major drawback is that synthetic materials do not degrade naturally in vivo. Thus, newly growing bone is obstructed by the artificial constructs, resulting in inflammed neighboring tissues.
A further major drawback of synthetic materials is that many synthetic materials can, and in many instances will, induce or elicit an inflammatory response.
There is thus a need to provide improved bone substitute material and bioresorbable skeletal constructs having sufficient compressive strength and load bearing capacity to be employed in load bearing applications without the drawbacks associated with metal, ceramic and polymeric materials.
It is therefore an object of the present invention to provide bone substitute material and bioresorbable skeletal constructs that overcome the foregoing and the other disadvantages associated with prior art bone substitution materials and prosthetic structures.
It is another object of the present invention to provide a novel extracellular matrix (ECM) based osteoinductive, biodegradable bone substitute material that promotes biocompatible osteoanagenesis.
It is another object of the present invention to provide a novel ECM based bone substitution material that is suitable for use in osteoanagenesis and bone morphogenesis.
It is another object of the present invention to provide a novel ECM based bone substitution material that exhibits satisfactory biocompatibility, osteoinductivity, osteoconductivity, biodegradability, with freedom from immunogenicity and toxicity to tissues.
It is yet another object of the present invention to provide artificial bioresorbable, skeletal constructs that promote angiogenesis.
It is yet another object of the present invention to provide artificial bioresorbable, osteoconductive and osteoinductive skeletal constructs that promote osteoanagenesis.
It is yet another object of the present invention to provide artificial bioresorbable, osteoconductive and osteoinductive skeletal constructs that function as delivery platforms for pharmacological agents and compositions.